|Publication number||US7063778 B2|
|Application number||US 10/501,440|
|Publication date||Jun 20, 2006|
|Filing date||Jan 14, 2003|
|Priority date||Jan 14, 2002|
|Also published as||DE60302544D1, DE60302544T2, EP1465729A1, EP1465729B1, US20050040035, WO2003057368A1|
|Publication number||10501440, 501440, PCT/2003/82, PCT/GB/2003/000082, PCT/GB/2003/00082, PCT/GB/3/000082, PCT/GB/3/00082, PCT/GB2003/000082, PCT/GB2003/00082, PCT/GB2003000082, PCT/GB200300082, PCT/GB3/000082, PCT/GB3/00082, PCT/GB3000082, PCT/GB300082, US 7063778 B2, US 7063778B2, US-B2-7063778, US7063778 B2, US7063778B2|
|Inventors||Moeketsi Mpholo, Benjamin Brown, Charles Gordon Smith|
|Original Assignee||Cambridge University Technical Services, Ltd.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (5), Non-Patent Citations (2), Referenced by (10), Classifications (22), Legal Events (5)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to the movement of very small volumes of fluids. In recent years there has been an increase in interest in the control of the movement of small volumes of fluid. This is because the movement of such small volumes is important in the field of biotechnology, as single cells and the fluid surrounding them need to be manipulated. Furthermore, micro machines are being developed for use in a wide number of fields, such as analytical probes, drug delivery systems and surgical tools. To perform these tasks it is necessary to pump fluids to provide a propulsion mechanism or in order to move materials held in the fluids.
A number of methods of moving small volumes of fluid have been proposed in the past. These include employment of thermal gradients, or electric or magnetic fields, as well as the employment of piezoelectric actuators.
Such systems are often complex to manufacture, however, and can be unreliable in terms of the level of control that they provide. Furthermore, most, if not all, are capable of directing fluids only in a single direction, which means that if they are to be employed for movement of fluid in different directions it is often necessary to duplicate components, which increases their overall complexity and cost and also reduces the reliability of the devices.
The present invention seeks to provide a device for moving small volumes of fluid which overcomes some of the above problems.
According to the present invention there is provided an apparatus for driving small volumes of fluid, the apparatus comprising:
a first array of electrically conductive electrodes formed on the substrate; and a second array of electrically conductive electrodes formed on the substrate, the first and second array being interlaced and being arranged such that each of the electrodes in the second array has a width in a fluid driving direction which is greater than that of each of the electrodes in the first array and such that the first and second set electrodes are positioned so that each of the electrodes of the first set is not at a position equidistant from adjacent electrodes of the second set, wherein both of electrodes have widths in the fluid flow direction and thickness selected such that, in use, by varying the peak nature of an alternating drive voltage applied thereto the direction of flow of a fluid adjacent to the arrays of electrodes can be controlled.
The present invention also provides means for providing a variable alternating voltage to the first and is second array of electrodes.
An insulator may be provided over at least a portion of one or both of the electrode arrays.
The fluid driving apparatus of the present invention may be arranged to drive fluid passing thereover in two opposite directions in order to provide a mixing effect.
The apparatus of the present invention may have a third set of electrodes having a width substantially identical to that of the first set, interlaced with the second set of electrode and separated from the first set by an insulator.
The present invention also provides a device for moving fluid by plug flow comprising two apparatus of the type defined above facing one another and defining a cavity therebetween.
The present invention may also provide a device for drawing fluids from two sources, mixing them and pumping them, the device comprising a first apparatus of the type described above; a second apparatus of the type defined above but having its electrodes arranged to be a mirror image of those of the first device; and a third apparatus of the type defined above positioned at the meeting point of the first and second apparatus.
The apparatus of the present invention may be configured to move elements, such as semiconductor components, within a fluid passing thereover.
The apparatus of the present invention may be employed to drive a micromachine.
The apparatus of the present invention may be arranged to be employed in a biochemical analysis process or drug manufacture process, or identify pathogens, bacteria or viruses.
A corresponding method is also provided.
Examples of the present invention will now be described with reference to the accompanying drawings, in which:
In use, a low voltage electric potential (usually less than 5 volts) is applied to the electrodes. The voltage is alternated at a frequency and so that the potential is low enough that ions in a fluid 7 above the surface of the electrodes 4, 6 can equilibrate locally. This usually means alternating the voltage in the kHz region for a monovalent salt solution. Upon application of the voltage potential the electrodes 4, 6 charge in a non-uniform manner to produce a gradient in potential parallel to the surface of the electrodes. This gradient drives the ions in the fluid 7 across the surface of the electrodes 4, 6 and the ions act through friction with the fluid to drag fluid molecules which produces a net fluid flow. The net fluid flow is caused by the anisotropic nature of related pairs of electrodes 4, 6.
What has been determined is that, by appropriate selection of the relative dimensions of the electrodes 4, 6 and the spacing therebetween, together with judicious selection of the magnitude of the voltage potential applied and the frequency thereof, the direction of flow of the fluid 7 can change dependent upon the frequency and amplitude of that applied voltage potential. Some discussion of the theory associated with this is set out below with reference to
However, it is believed that the generation of a reversible flow can be explained by considering the electrical circuit equivalent of the electrodes dissolution to be a capacitor equivalent to the large electrode, a resistor and a second capacitor (equivalent to that of the adjacent smaller electrode) in series. With a double layer over each electrode, if an AC potential is applied to this then there is a potential voltage across the double layer over the small electrode that is always larger than that over the large electrode by an amount equal to the ratio of widths of the two electrodes. This is because the area of the small electrode is k times smaller (assuming equal length of electrodes) providing a capacitance that is k times smaller. As the amplitude of the AC potential is increased the voltage across the double layers above each electrode also increases. Eventually an amplitude is reached where the potential across the double layer on the small electrode is equal to the ionisation potential of the fluid above the electrode. At this point the capacitance of the double layer starts to break down and charge flows across it. In other words, charge is injected into the fluid over the small electrode. This charge will be opposite to the charge on the ions in the double layer already, and so the charges will neutralise these ions. If the fluid is water, for example, this will create oxygen and hydrogen, but in sufficiently low concentrations that they simply dissolve and diffuse away. At the larger electrode the potential drop across the double layer is not large enough to ionise the water and so ions are stored in the double layer. When the applied potential is reversed on the other half of the applied AC signal, the charges above the large electrode will move along the field lines towards the small electrode. The charges over the small electrode will move towards the large electrode. However, far fewer ions are on the small electrode given the neutralisation process, and thus the bulk flow of ions is from the large electrode to the small electrode. The flow of ions drags the fluid with it and causes movement, which is the observed pumping.
Accordingly, it is possible for the example devices of
In order to increase the flexibility of the device (in terms of its ability to control different fluids having differing properties and to increase the control of fluid flow), certain adaptations can be made to the examples described above.
In an example device which has electrode dimensions of the type discussed with reference to the examples of
Insulator covered electrodes offer numerous advantages. In the current design where electrodes are exposed directly to water, the maximum fluid velocity that can be achieved is limited by the maximum voltage that can be placed across the double layer before ionisation of the solution starts to occur. This maximum fluid velocity can be increased by placing an insulating layer over the surface of the electrodes. Following is a simple model that explains why this is the case.
The velocity of the fluid over the surface of an electrode is proportional to both the mobile charge in the double layer and the potential gradient or field parallel to the electrode surface, above the double layer.
These two factors are affected at a voltage just before ionisation of the solution starts by an insulating layer placed on the surface of the electrodes. If an insulating layer is introduced over the surface of the electrodes then a higher voltage can be applied to the device before ionisation of the solution occurs. However, the mobile charge in the double layer that gives rise to the pumping mechanism is still proportional to the voltage across the double layer. Thus just before ionisation of the solution the mobile charge within the double layer is the same as it was with no insulating layer.
However, the field above the double layer parallel to the electrode surface is not the same as it was without the insulating layer. This field is proportional to the potential drop from the electrode to the point above the double layer. In the case with no insulating layer this is simply given by the charge in the double layer divided by the capacitance of the double layer. If an insulating layer is present this potential drop is now across both the capacitance of the double layer and the capacitance of the insulating layer. Since these two capacitances are in series, their combined capacitance will be smaller than the capacitance of the double layer. The potential drop is given by the charge in the double layer divided by this capacitance and will thus be larger for a given charge in the double layer. Thus at the applied voltage just before ionisation of the solution, the field above the double layer parallel to the electrodes will be larger than when no insulating layer is present. The larger field will give rise to a larger fluid velocity or reversed direction of flow, dependent upon conditions such as fluid type, applied voltage or electrode dimension.
From the above model it is clear that the lower the capacitance of the double layer the greater the fluid velocity that can be achieved. However the above model makes various approximations and simplifications which will provide an upper limit to the optimal thickness. The finite size of the electrodes will reduce the maximum possible velocity, as the thickness of the insulating layer become a significant fraction of the electrode size. The required driving voltage will also increase as the thickness of the insulating layer is increased.
Theoretically it has been shown that smaller electrode sizes should provide higher velocities.
The frequency that gives the maximum average velocity is given by ω0/√(XminXmax). Hence, the maximum velocity is mainly a function of electrode size and the supplied voltage.
We have shown that smaller electrode size increases the velocity by a factor of about 2 by reducing the electrode size by the same factor. This paves a way to very narrow channels that can pump at very high velocities.
The object is propelled from below through the boundary layer that will form around the object. Since in this invention the flow profile 27 is such that the velocity decreases with height above the electrodes, this means there is a decrease in pressure from where the object is floating to the electrode surface. This aids in pinning the object in its course as the pressure differences on the sides could cause it to rotate or move sideways. The object is seen to move in a straight line.
If the object is propelled to the centre of the arrangement shown in
As the electrodes are capable of driving the fluid in the forward and backward direction, we have observed the objects going at velocities well above 100 μm/s in both directions.
Another example of the invention, that could be used to react two different chemicals or biological substances dissolved in a fluid, is shown in
After some time the resulting reactants are observed to see that the proteins had markers attached in the sections where the flows had been brought together. The central region 30 has two sets of electrodes that can pump fluids at different velocities in the same or opposite directions, by control of their drive voltages, in the manner discussed above. The smaller molecules can then diffuse across from one flow region to the next, while the larger proteins do not have time to diffuse in the opposite is direction. As a result it can ensure that there are enough of the smaller markers supplied to fully react with the larger molecules.
It could be that the smaller molecules fluoresce and bind to the larger protein molecules (that could be proteins) making them fluoresce under UV light. We can then observe if the proteins fluoresce.
If a user were looking to identify smaller molecules or particles such as a virus, then the virus can be bound with a larger molecule or colloidal particle before exposing the target substance to the fluorescent markers.
Rather than have an observer identify the fluorescence as is commonly employed now, UV light source 31 illuminates the resulting products and the current in a photo-diode 32 observed under the reactants on the same chip. The photodiode 23 has a filter 33 that only lets light through at the wavelength of the fluorescent molecules. The diode 32 may, for example, be a silicon diode defined using semiconductor processing directly under the electrodes that do the pumping. The electrodes can also be defined using silicon chip technology and could be made from TiN (Titanium nitride), or Al or Ti,or Tu. The filter 33 is made using layers of thin semitransparent metal (TiN) with a transparent insulator (silicon nitride or silicon dioxide) in between in the manner of a Fabry Perot interferometer.
The current generated in the diode 32 depends on the amount of fluorescent markers which depends on the number of larger molecules. The circuitry in the chip under the electrodes is designed to detect this current and give an electrical signal out of the chip to indicate the amount of target molecules present.
The above structure can have pumping electrodes at the top and the bottom separated by a 100 micron spacer. The channels can be around 1 mm wide. These dimensions can be smaller but larger values to keep the costs of fabrication down.
Because the invention can not be used to introduce fluid into a region containing a gas, we must prepare the chip by immersing it in an ionic solution that will not react with the reagents. For many examples a slightly salty water solution is acceptable. This immersion procedure is performed in an ultrasonic bath to ensure that no bubbles are left behind. The top of the device then has a removable flexible film stuck over the holes to keep the chip clean until it is needed. To prevent the build up of back pressure on the fluids being pumped it must be ensured that the volume of the reservoirs above the holes is large in comparison to the volume of the reaction chambers and channels (tens of nanoleters).
A more integrated solution (shown in
The invention can provide mixing on a microscopic scale. This is very hard to do with prior art devices, but the invention can be employed can do this on very small length scales of a few tens of microns. This allow the speeding up of many reactions which are at the moment diffusion limited.
One technique for mixing uses four pairs of electrodes arranged to pump liquid in four different directions at right angles to each other. Such an arrangement is shown in
The electrodes are marked in grey and the arrows show the fluid flow over each region if they are all operated with the same AC voltage applied across pairs of electrodes.
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|U.S. Classification||204/547, 204/643|
|International Classification||B01L3/00, F04B19/00, G01N35/08, G01N37/00, B01F13/00, B01F5/00, B01J19/00, G01N27/447, B81B1/00|
|Cooperative Classification||B01L2300/0887, B01L3/502707, F04B19/006, B01F13/0076, B01L3/50273, B01L2400/0415, B01L3/502784|
|European Classification||B01L3/5027J4, B01L3/5027D, F04B19/00M, B01F13/00M6A|
|Mar 14, 2005||AS||Assignment|
Owner name: CAMBRIDGE UNIVERSITY TECHNICAL SERVICES, LTD., UNI
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:MPHOLO, MOEKETSI;BROWN, BENJAMIN;SMITH, CHARLES GORDON;REEL/FRAME:015769/0180
Effective date: 20040623
|Nov 18, 2009||FPAY||Fee payment|
Year of fee payment: 4
|Jan 31, 2014||REMI||Maintenance fee reminder mailed|
|Jun 20, 2014||LAPS||Lapse for failure to pay maintenance fees|
|Aug 12, 2014||FP||Expired due to failure to pay maintenance fee|
Effective date: 20140620